Synthesis and evaluation of 1,3,4-oxadiazole derivatives for development as broad-spectrum antibiotics |
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| Institution: | 1. Univ. Rennes, INSERM, Chemistry Oncogenesis Stress Signaling (COSS) Group U1242, 35000 Rennes, France;2. Université de Caen Normandie, EA4655 U2RM, Antibio-résistance Group, Caen, France;3. Univ. Rennes, CNRS, Institut de Génétique et Développement de Rennes (IGDR) UMR6290, 35000 Rennes, France;1. Department of Chemistry, The Oxford College of Engineering, Bangalore (Karnataka) -560068, India;2. Department of Chemistry, Regional Ayurveda Research Institute for Drug Development, Gwalior (M.P.) – 474009, India;3. Department of Biotechnology, Lovely Professional University, Jalandhar (Punjab) – 144111, India;4. Regional Advanced Water Testing Laboratory, Mohali (Punjab) -160059, India;5. Punjab Biotechnology Incubators, Mohali (Punjab) -160059, India;1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P Marg, Matunga (East), Mumbai 400019, India;2. SVKM’s Dr. Bhanuben Nanavati College of Pharmacy, Gate No. 1, Mithibai College Campus, V.M. Road, Vile Parle (West), Mumbai 400056, India;1. Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;2. Department of Biotechnology, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;3. Department of Botany, Sri Venkateswara University, Tirupati 517 502, Andhra Pradesh, India;1. Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University, 575 Stadium Mall Dr, West Lafayette, IN, 47907, USA;2. Purdue Institute for Drug Discovery, Purdue University, West Lafayette, IN, 47907, USA;3. Purdue Institute for Integrative Neuroscience, Purdue University, West Lafayette, IN, 47907, USA;1. Departmento de Quimica, FCTUC, Universidade de Coimbra, Rua Larga, Coimbra 3004-535, Portugal;2. Department of Oral Biological Sciences, University of Witwatersrand, 7 York Road, Parktown, Johannesburg 2193, South Africa;3. Department of Chemistry, Faculty of Science, Taibah University, PO Box 30002, Al Madinah Al Munawarrah, Saudi Arabia |
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| Abstract: | The reality and intensity of antibiotic resistance in pathogenic bacteria calls for the rapid development of new antimicrobial drugs. In bacteria, trans-translation is the primary quality control mechanism for rescuing ribosomes arrested during translation. Because trans-translation is absent in eukaryotes but necessary to avoid ribosomal stalling and therefore essential for bacterial survival, it is a promising target either for novel antibiotics or for improving the activities of the protein synthesis inhibitors already in use. Oxadiazole derivatives display strong bactericidal activity against a large number of bacteria, but their effects on trans-translation were recently questioned. In this work, a series of new 1,3,4-oxadiazole derivatives and analogs were synthesized and assessed for their efficiency as antimicrobial agents against a wide range of gram-positive and gram-negative pathogenic strains. Despite the strong antimicrobial activity observed in these molecules, it turns out that they do not target trans-translation in vivo, but they definitely act on other cellular pathways. |
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| Keywords: | Antibiotics Oxadiazoles Ribosome tmRNA |
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